Comprehensive Hearing Loss and Deafness Panel

Last modified: Mar 21, 2018


  • Is a 181 gene panel that includes assessment of non-coding variants
  • Is ideal for patients with a clinical suspicion of syndromic or non-syndromic genetic hearing loss.

Analysis methods

  • PLUS
  • SEQ


3-4 weeks

Number of genes


Test code


CPT codes

SEQ 81430
DEL/DUP 81431


The Blueprint Genetics Comprehensive Hearing Loss and Deafness Panel (test code EA0501):

  • Is a 181 gene panel that includes assessment of selected non-coding disease-causing variants
  • Is available as PLUS analysis (sequencing analysis and deletion/duplication analysis), sequencing analysis only or deletion/duplication analysis only

ICD codes

Commonly used ICD-10 code(s) when ordering the Comprehensive Hearing Loss and Deafness Panel

ICD-10 Disease
E70.30 Waardenburg syndrome
Q87.89 Alport syndrome
H90.5 Sensorineural hearing loss, unilateral and bilateral
E07.1 Pendred syndrome
H35.50 Usher syndrome
Q89.8 Stickler syndrome
Q87.89 Branchio-oto-renal (BOR) syndrome

Sample Requirements

  • EDTA blood, min. 1 ml
  • Purified DNA, min. 3μg
  • Saliva (Oragene DNA OG-500 kit)

Label the sample tube with your patient’s name, date of birth and the date of sample collection.

Note that we do not accept DNA samples isolated from formalin-fixed paraffin-embedded (FFPE) tissue.

Subpanel description

This comprehensive panel includes genes from the following panels: Alport Syndrome Panel, Branchio-Oto-Renal (BOR) Syndrome Panel, Non-Syndromic Hearing Loss Panel, Pendred Syndrome Panel, Stickler Syndrome Panel, Syndromic Hearing Loss Panel, Usher Syndrome Panel and Waardenburg Syndrome Panel.

Hearing loss is a genetically very heterogenous group of phenotypes varying in severity and causes. Non-syndromic sensorineural hearing loss is a partial or total loss of hearing that occurs without other associated clinical findings. In syndromic hearing loss, symptoms affecting other parts of the body occur in addition to hearing impairment or deafness. Sensorineural hearing loss can be unilateral or bilateral and it can be stable or progressive. In addition, the loss may appear with various intensivity to high, middle or low tones. It is estimated that approximately 60-80% of congenital hearing loss is genetic in origin. Some 60%-to-70% of congenital hereditary hearing impairnment have a non-syndromic origin. The prevalence of non-syndromic hearing loss is 3-4:10,000 neonates and increases with age. In many populations, mutations in GJB2 are the most prevalent explaining up to 50% of all non-syndromic hearing losses. Altogether syndromic hearing loss accounts for 20% to 30% of congenital hearing loss and deafness and the combined prevalence of syndromic hearing loss is approximately 1-2:10,000.

Genes in the Comprehensive Hearing Loss and Deafness Panel and their clinical significance

Gene Associated phenotypes Inheritance ClinVar HGMD
ABHD12 Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract AR 12 18
ACTG1* Deafness, Baraitser-Winter syndrome AD 21 43
ADCY1 Deafness AR 1 1
ADGRV1 Usher syndrome, Febrile seizures, familial, 4 AR/Digenic 58 164
AIFM1 Deafness XL 27 23
ALMS1* Alström syndrome AR 50 291
ANKH Calcium pyrophosphate deposition disease (familial chondrocalcinosis type 2), Craniometaphyseal dysplasia autosomal dominant type AD 12 20
ATP6V1B1 Renal tubular acidosis with deafness AR 9 54
ATP6V1B2 Deafness, congenital, with onychodystrophy, autosomal dominant, Zimmermann-Laband syndrome 2 AD 5 2
BCS1L Bjornstad syndrome AR 32 37
BDP1* Hearing loss AD/AR 1
BSND Sensorineural deafness with mild renal dysfunction, Bartter syndrome AR 10 19
BTD Biotinidase deficiency AR 183 235
C10ORF2 Perrault syndrome, Mitochondrial DNA depletion syndrome AR 37
CABP2 Deafness AR 1 6
CACNA1D Primary aldosteronism, seizures, and neurologic abnormalities, Sinoatrial node dysfunction and deafness AD/AR 6 5
CCDC50 Deafness AD 1 4
CD151 Raph blood group BG 1
CD164 Deafness, autosomal dominant 66 1
CDC14A Deafness, autosomal recessive 105 2 2
CDH23 Deafness, Usher syndrome AR/Digenic 69 332
CDKN1C Beckwith-Wiedemann syndrome, IMAGE syndrome AD 24 81
CEACAM16 Deafness AD 3 4
CEP78 Cone rod dystrophy and hearing loss 7 8
CHD7 Isolated gonadotropin-releasing hormone deficiency, CHARGE syndrome AD 192 784
CHSY1 Temtamy preaxial brachydactyly syndrome AR 6 11
CIB2 Deafness, Usher syndrome AR 4 15
CLDN14 Deafness AR 10 12
CLIC5 Deafness AR 1 1
CLPP Deafness AR 3 13
CLRN1 Retinitis pigmentosa, Usher syndrome AR 17 34
COCH Deafness AD 10 28
COL2A1 Avascular necrosis of femoral head, Rhegmatogenous retinal detachment, Epiphyseal dysplasia, with myopia and deafness, Czech dysplasia, Achondrogenesis type 2, Platyspondylic dysplasia Torrance type, Hypochondrogenesis, Spondyloepiphyseal dysplasia congenital (SEDC), Spondyloepimetaphyseal dysplasia (SEMD) Strudwick type, Kniest dysplasia, Spondyloperipheral dysplasia, Mild SED with premature onset arthrosis, SED with metatarsal shortening, Stickler syndrome type 1 AD 138 541
COL4A3 Alport syndrome, Hematuria, benign familial AD/AR 34 229
COL4A4 Alport syndrome AD/AR 21 184
COL4A5 Alport syndrome XL 645 940
COL4A6 Deafness, with cochlear malformation XL 11 4
COL9A1 Stickler syndrome recessive type, Multiple epiphyseal dysplasia type 6 (EDM6) AR 7 5
COL9A2 Stickler syndrome, Multiple epiphyseal dysplasia type 2 (EDM2) AD/AR 7 12
COL9A3 Multiple epihyseal dysplasia type 3 (EDM3) AD/AR 6 15
COL11A1 Marshall syndrome, Fibrochondrogenesis, Stickler syndrome type 2 AD/AR 22 81
COL11A2 Weissenbacher-Zweymuller syndrome, Deafness, Otospondylomegaepiphyseal dysplasia, Fibrochondrogenesis, Stickler syndrome type 3 (non-ocular) AD/AR 23 54
CRYM Deafness AD 2 3
DCAF17 Woodhouse-Sakati syndrome AR 12 13
DCDC2 Deafness AR 9 9
DFNA5 Deafness AD 6 9
DFNB31 Deafness, Usher syndrome AR 11 30
DFNB59 Deafness AR 7 20
DIABLO Deafness AD 1 2
DIAPH1 Deafness AD 7 15
DIAPH3 Non-syndromic sensorineural deafness AD/AR 1 6
DLX5 Split-hand/foot malformation with sensorineural hearing loss AR 3 8
DNMT1 Neuropathy, hereditary sensory, Cerebellar ataxia, deafness, and narcolepsy AD 10 19
DSPP Dentin dysplasia, Dentinogenesis imperfecta, Deafness, with dentinogenesis imperfecta AD 9 47
EDN3 Hirschsprung disease, Central hypoventilation syndrome, congenital, Waardenburg syndrome AD/AR 6 21
EDNRB Hirschsprung disease, ABCD syndrome, Waardenburg syndrome AD/AR 7 66
ELMOD3 Deafness AR 1 1
EPS8 Deafness AR 1 2
EPS8L2 Deafness, autosomal recessive 106 2
ESPN* Deafness AD/AR 8 12
ESRRB Deafness AR 10 17
EYA1 Otofaciocervical syndrome, Branchiootic syndrome, Branchiootorenal syndrome AD 39 197
EYA4 Dilated cardiomyopathy (DCM) AD 9 24
FAM65B Deafness AR 1 2
FDXR Auditory neuropathy and optic atrophy AR 4
FGF3 Deafness, congenital with inner ear agenesis, microtia, and microdontia AR 13 20
FGFR3 Lacrimoauriculodentodigital syndrome, Muenke syndrome, Crouzon syndrome with acanthosis nigricans, Camptodactyly, tall stature, and hearing loss (CATSHL) syndrome, Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia type 1, Thanatophoric dysplasia type 2, SADDAN AD/AR 53 70
FOXI1 Pendred syndrome, Enlarged vestibular aqueduct AR 1 9
GATA3 Hypomagnesemia, renal AD 20 77
GIPC3 Deafness AR 9 18
GJA1* Oculodentodigital dysplasia mild type, Oculodentodigital dysplasia severe type, Syndactyly type 3 AD/AR 28 105
GJB2 Deafness, Bart-Pumphrey syndrome, Keratoderma, palmoplantar, with deafness, Vohwinkel syndrome, Hystrix-like ichthyosis with deafness, Keratitis-icthyosis-deafness syndrome AD/AR/Digenic 111 393
GJB3 Deafness AD/Digenic 10 38
GJB6 Deafness AR/Digenic 9 28
GPSM2 Deafness, Chudley-McCullough syndrome AR 14 11
GRHL2 Ectodermal dysplasia/short stature syndrome AD/AR 8 9
GRXCR1 Deafness AR 4 9
GRXCR2 Deafness AR 1 2
HARS* Usher syndrome, Charcot-Marie-Tooth disease, axonal, type 2W AR 5 9
HARS2 Perrault syndrome AR 7 3
HGF Deafness AR 4 10
HOMER2 Deafness AD 2
HOXB1 Facial paresis, hereditary congenital AR 1 5
HSD17B4 Perrault syndrome AR 41 96
ILDR1 Deafness AR 4 23
KARS Charcot-Marie-Tooth disease AR 7 20
KCNE1 Long QT syndrome, Jervell and Lange-Nielsen syndrome AD/AR/Digenic 8 45
KCNJ10 Seizures, sensorineural deafness, ataxia, mental retardation, and electrolyte imbalance (SESAME syndrome), Pendred syndrome, Enlarged vestibular aqueduct AR/Digenic 14 24
KCNQ1 Short QT syndrome, Long QT syndrome, Atrial fibrillation, Jervell and Lange-Nielsen syndrome AD/AR/Digenic 258 599
KCNQ4 Deafness AD 26 37
KIT Gastrointestinal stromal tumor AD 73 109
LARS2 Perrault syndrome AR 11 11
LHFPL5 Deafness AR 6 10
LOXHD1 Deafness AR 14 47
LRP2 Donnai-Barrow syndrome, Faciooculoacousticorenal syndrome AR 22 27
LRTOMT Deafness AR 7 16
MAN2B1 Mannosidosis, alpha B, lysosomal AR 34 142
MANBA Mannosidosis, lysosomal AR 12 18
MARVELD2 Deafness AR 7 17
MET Deafness, Renal cell carcinoma, papillary AD/AR 20 24
MGP Keutel syndrome AR 5 7
MIR96 Deafness AD 2 4
MITF Renal cell carcinoma with or without malignant melanoma, Tietz albinism-deafness syndrome, Waardenburg syndrome, Melanoma, cutaneous malignant AD 24 55
MSRB3 Deafness AR 4 2
MYH9 Sebastian syndrome, May-Hegglin anomaly, Epstein syndrome, Fechtner syndrome, Macrothrombocytopenia and progressive sensorineural deafness AD 21 113
MYH14 Deafness, Peripheral neuropathy, myopathy, hoarseness, and hearing loss AD 6 36
MYO3A Deafness AR 7 19
MYO6 Deafness, Deafness, autosomal dominant, 22 AR 17 58
MYO7A Deafness, Usher syndrome AD/AR 155 426
MYO15A Deafness AR 66 221
NARS2 Combined oxidative phosphorylation deficiency AR 9 12
NDP Exudative vitreoretinopathy, Norrie disease XL 29 159
NLRP3 Neonatal onset multisystem inflammatory disease (NOMID), Muckle-Wells syndrome, Chronic infantile neurologic cutaneous articular (CINCA) syndrome AD 19 127
OSBPL2 Deafness AD 2 3
OTOA*,# Deafness AR 16 26
OTOF Neuropathy, Deafness AR 98 160
OTOG Deafness AR 6 3
OTOGL Deafness AR 16 19
P2RX2 Deafness AD 2 4
PAX3 Craniofacial-deafness-hand syndrome, Waardenburg syndrome AD/AR 22 135
PCDH15 Deafness, Usher syndrome AR/Digenic 71 107
PDZD7 Usher syndrome Digenic 1 15
PEX1 Heimler syndrome AR 77 130
PEX6 Heimler syndrome AR 25 105
PEX26 Adrenoleukodystrophy, neonatal, Zellweger syndrome, Peroxisome biogenesis disorder AR 11 24
PNPT1*,# Deafness, Combined oxidative phosphorylation deficiency, 13 AR 9 6
POLR1C Treacher Collins syndrome AR 16 20
POLR1D Treacher Collins syndrome AD/AR 7 26
POU3F4 Deafness XL 23 74
POU4F3 Deafness AD 8 31
PRPS1* Deafness, Phosphoribosylpyrophosphate synthetase I superactivity, Arts syndrome, Charcot-Marie-Tooth disease, X-linked recessive, 5, Nonsyndromic sensorineural deafness, 2, X-linked XL 22 27
RDX* Deafness AR 6 8
RMND1* Combined oxidative phosphorylation deficiency AR 15 15
RPS6KA3 Coffin-Lowry syndrome, Mental retardation XL 47 165
S1PR2 Deafness, autosomal recessive 68 2 2
SALL1* Townes-Brocks syndrome 1 AD 24 83
SALL4 Acro-renal-ocular syndrome, Duane-radial ray/Okohiro syndrome AD 17 50
SEMA3E CHARGE syndrome AD 1 4
SERPINB6 Deafness AR 1 3
SIX1 Deafness, Branchiootic syndrome, Branchiootorenal syndrome AD 11 16
SIX5 Branchiootorenal syndrome AD 3 9
SLC17A8 Deafness AD 1 7
SLC19A2 Thiamine-responsive megaloblastic anemia syndrome AR 11 49
SLC26A4 Deafness, Pendred syndrome, Enlarged vestibular aqueduct AR 137 535
SLC26A5 Deafness AR 2 7
SLC29A3 Histiocytosis-lymphadenopathy plus syndrome, Dysosteosclerosis AR 16 23
SLC33A1* Congenital cataracts, hearing loss, and neurodegeneration, Spastic paraplegia 42, autosomal dominant AR 6 7
SLC52A2 Brown-Vialetto-Van Laere syndrome AR 22 19
SLC52A3 Fazio-Londe disease, Brown-Vialetto-Van Laere syndrome AR 33 30
SLITRK6 Deafness and myopia AR 3 3
SMAD4 Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome, Polyposis, juvenile intestinal, Myhre dysplasia, Hereditary hemorrhagic telangiectasia AD 139 132
SMPX Deafness XL 7 12
SNAI2 Waardenburg syndrome AR 2 4
SOX10 Peripheral demyelinating neuropathy, central dysmyelination, Waardenburg syndrome, and Hirschsprung disease AD 34 133
SPATA5 Schizophrenia AR 16 21
STRC*,# Deafness AR 25 77
SUCLA2 Mitochondrial DNA depletion syndrome AR 8 27
SUCLG1 Mitochondrial DNA depletion syndrome AR 11 28
SYNE4 Deafness AR 4 1
TBC1D24 Deafness, Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS) syndrome AD/AR 42 49
TCOF1 Treacher Collins syndrome AD 31 320
TECTA Deafness AD/AR 23 111
TFAP2A Branchiooculofacial sydrome AD 9 41
TIMM8A* Mohr-Tranebjaerg syndrome, Jensen syndrome, Opticoacoustic nerve atrophy with dementia XL 10 21
TJP2 Cholestasis, progressive familial intrahepatic, Hypercholanemia, familial AR 20 23
TMC1 Deafness AR 24 85
TMEM132E Hearing loss AD/AR 1
TMIE Deafness AR 9 10
TMPRSS3 Deafness AR 23 79
TNC Deafness AD 3 3
TPRN Deafness AR 5 11
TRIOBP Deafness AR 17 35
TRMU Liver failure, infantile, Reversible infantile respiratory chain deficiency AR 18 17
TSPEAR* Deafness AR 1 7
TYR* Albinism, oculocutaneous AR 69 391
USH1C Deafness, Usher syndrome AR 18 48
USH1G Usher syndrome AR 9 26
USH2A Usher syndrome, Retinitis pigmentosa, Retinitis pigmentosa 39 AR 225 1001
VCAN Wagner disease AD 11 19
WBP2 Deafness, autosomal recessive 107 3 3
WFS1 Wolfram syndrome, Deafness AD/AR 65 343

* Some, or all, of the gene is duplicated in the genome. Read more.

# The gene has suboptimal coverage (means <90% of the gene’s target nucleotides are covered at >20x with mapping quality score (MQ>20) reads).

The sensitivity to detect variants may be limited in genes marked with an asterisk (*) or number sign (#)

Gene refers to the HGNC approved gene symbol; Inheritance refers to inheritance patterns such as autosomal dominant (AD), autosomal recessive (AR), X-linked (XL), X-linked dominant (XLD) and X-linked recessive (XLR); ClinVar refers to the number of variants in the gene classified as pathogenic or likely pathogenic in this database (ClinVar); HGMD refers to the number of variants with possible disease association in the gene listed in Human Gene Mutation Database (HGMD). The list of associated, gene specific phenotypes are generated from CGD or Orphanet databases.

Non-coding variants covered by the panel

Gene Genomic location HG19 HGVS RefSeq RS-number
ANKH Chr5:14871567 c.-11C>T NM_054027.4
BCS1L Chr2:219524871 c.-147A>G NM_004328.4
BCS1L Chr2:219525123 c.-50+155T>A NM_004328.4 rs386833855
BTD Chr3:15687154 c.*159G>A NM_000060.2 rs530872564
CDH23 Chr10:73403617 c.1135-1G>T NM_022124.5
CDKN1C Chr11:2905209 c.*5+20G>T NM_000076.2 rs760540648
CHD7 Chr8:61734568 c.2836-15C>G NM_017780.3
CHD7 Chr8:61757794 c.5051-15T>A NM_017780.3
CHD7 Chr8:61763035 c.5405-17G>A NM_017780.3 rs794727423
COL11A1 Chr1:103488576 c.1027-24A>G NM_080629.2
COL11A1 Chr1:103386637 c.3744+437T>G NM_080629.2
COL11A1 Chr1:103491958 c.781-450T>G NM_080629.2 rs587782990
COL2A1 Chr12:48379984 c.1527+135G>A NM_001844.4
COL4A3 Chr2:228145145 c.2224-11C>T NM_000091.4
COL4A3 Chr2:228168708 c.4028-27A>G NM_000091.4
COL4A3 Chr2:228173092 c.4462+457C>G NM_000091.4
COL4A3 Chr2:228176114 c.4929-388G>T NM_000091.4
COL4A4 Chr2:227875240 c.4334-23A>G NM_000092.4
COL4A5 ChrX:107838719 c.1424-20T>A NM_033380.2 rs281874668
COL4A5 ChrX:107849958 c.2245-14T>A NM_033380.2
COL4A5 ChrX:107852872 c.2395+2750A>G NM_033380.2
COL4A5 ChrX:107813924 c.385-719G>A NM_033380.2 rs104886396
COL4A5 ChrX:107933678 c.4529-2300T>G NM_033380.2
COL4A5 ChrX:107935633 c.4529-345A>G NM_033380.2
COL4A5 ChrX:107816792 c.466-12G>A NM_033380.2 rs104886414
COL4A5 ChrX:107816787 c.466-17T>G NM_033380.2 rs104886415
COL4A5 ChrX:107938272 c.4821+121T>C NM_033380.2 rs104886423
COL4A5 ChrX:107938346 c.4822-151_4822-150insT NM_033380.2 rs397515494
DIAPH3 Chr13:60738072 c.-172G>A NM_001042517.1
EDN3 Chr20:57875743 c.-125G>A NM_000114.2
EDN3 Chr20:57875849 c.-19C>A NM_000114.2 rs375594972
EYA1 Chr8:72156939 c.1051-12T>G NM_000503.4
EYA1 Chr8:72211483 c.640-15G>A NM_000503.4
EYA4 Chr6:133833847 c.1282-12T>A NM_004100.4
EYA4 Chr6:133833997 c.1341-19T>A NM_004100.4
GJB2 Chr13:20763744 c.-22-2A>C NM_004004.5 rs201895089
GJB2 Chr13:20766921 c.-23+1G>A NM_004004.5 rs80338940
GJB2 Chr13:20766922 c.-23G>T NM_004004.5 rs786204734
GJB2 Chr13:20767158 c.-259C>T NM_004004.5
GJB2 Chr13:20767159 c.-260C>T NM_004004.5
GRXCR1 Chr4:42965170 c.627+19A>T NM_001080476.2 rs201824235
KCNJ10 Chr1:160039811 c.-1+1G>T NM_002241.4 rs796052606
MYO3A Chr10:26409593 c.1777-12G>A NM_017433.4
MYO6 Chr6:76593963 c.2417-1758T>G NM_004999.3
MYO7A Chr11:76839534 c.-48A>G NM_000260.3
MYO7A Chr11:76893448 c.3109-21G>A NM_000260.3
NDP ChrX:43818099 c.-207-1G>A NM_000266.3
NDP ChrX:43832549 c.-208+1G>A NM_000266.3
NDP ChrX:43832548 c.-208+2T>G NM_000266.3
NDP ChrX:43832545 c.-208+5G>A NM_000266.3
PAX3 Chr2:223085913 c.958+28A>T NM_181459.3
PCDH15 Chr10:56560684 c.-29+1G>C NM_001142763.1
PEX6 Chr6:42933952 c.2300+28G>A NM_000287.3 rs267608237
PEX6 Chr6:42933858 c.2301-15C>G NM_000287.3 rs267608236
RPS6KA3 ChrX:20191268 c.1228-279T>G NM_004586.2
RPS6KA3 ChrX:20213274 c.326-11A>G NM_004586.2
SLC26A4 Chr7:107301201 c.-103T>C NM_000441.1 rs60284988
SLC26A4 Chr7:107301301 c.-4+1G>C NM_000441.1
SLC26A4 Chr7:107301305 c.-4+5G>A NM_000441.1 rs727503425
SLC26A4 Chr7:107301244 c.-60A>G NM_000441.1 rs545973091
SLC26A4 Chr7:107334836 c.1264-12T>A NM_000441.1
SLC26A4 Chr7:107336364 c.1438-7dupT NM_000441.1 rs754734032
SOX10 Chr22:38412215 c.-31954C>T NM_006941.3 rs606231342
SOX10 Chr22:38379877 c.-84-2A>T NM_006941.3
TIMM8A ChrX:100601671 c.133-23A>C NM_004085.3 rs869320666
TMC1 Chr9:75315577 c.362+18A>G NM_138691.2
TYR Chr11:88960973 c.1037-18T>G NM_000372.4
USH2A Chr1:216596610 c.-259G>T NM_206933.2
USH2A Chr1:215821092 c.14583-20C>G NM_206933.2
USH2A Chr1:216247476 c.5573-834A>G NM_206933.2
USH2A Chr1:216064540 c.7595-2144A>G NM_206933.2 rs786200928
USH2A Chr1:216039721 c.8845+628C>T NM_206933.2
USH2A Chr1:215967783 c.9959-4159A>G NM_206933.2
WFS1 Chr4:6271704 c.-43G>T NM_006005.3

Added and removed genes from the panel

Genes added Genes removed

Test strength

The strengths of this test include:
  • CAP and ISO-15189 accreditations covering all operations at Blueprint Genetics including all Whole Exome Sequencing, NGS panels and confirmatory testing
  • CLIA-certified personnel performing clinical testing in a CLIA-certified laboratory
  • Powerful sequencing technologies, advanced target enrichment methods and precision bioinformatics pipelines ensure superior analytical performance
  • Careful construction of clinically effective and scientifically justified gene panels
  • Our Nucleus online portal providing transparent and easy access to quality and performance data at the patient level
  • Our publically available analytic validation demonstrating complete details of test performance
  • 1479 non-coding disease causing variants in Blueprint WES assay (please see below ‘Non-coding disease causing variants covered by this panel’)
  • Our rigorous variant classification based on modified ACMG variant classification scheme
  • Our systematic clinical interpretation workflow using proprietary software enabling accurate and traceable processing of NGS data
  • Our comprehensive clinical statements

Test limitations

The following exons are not included in the panel as they are not sufficiently covered with high quality sequence reads: OTOA (22-27), OTOGL (21), STRC (1-15). Genes with suboptimal coverage in our assay are marked with number sign (#) and genes with partial, or whole gene, segmental duplications in the human genome are marked with an asterisk (*) if they overlap with the UCSC pseudogene regions. Gene is considered to have suboptimal coverage when >90% of the gene's target nucleotides are not covered at >20x with mapping quality score (MQ>20) reads. The technology may have limited sensitivity to detect variants in genes marked with these symbols (please see the Panel content table above).

This test does not detect the following:
  • Complex inversions
  • Gene conversions
  • Balanced translocations
  • Mitochondrial DNA variants
  • Repeat expansion disorders unless specifically mentioned
  • Non-coding variants deeper than ±20 base pairs from exon-intron boundary unless otherwise indicated (please see above Panel Content / non-coding variants covered by the panel).

This test may not reliably detect the following:

  • Low level mosaicism
  • Stretches of mononucleotide repeats
  • Indels larger than 50bp
  • Single exon deletions or duplications
  • Variants within pseudogene regions/duplicated segments

The sensitivity of this test may be reduced if DNA is extracted by a laboratory other than Blueprint Genetics.

For additional information, please refer to the Test performance section and see our Analytic Validation.

The Blueprint Genetics comprehensive hearing loss and deafness panel covers classical genes associated with Waardenburg syndrome, Alport syndrome, sensorineural hearing loss, unilateral and bilateral, non-syndromic genetic deafness, Pendred syndrome, Usher syndrome, Stickler syndrome, Jervell and Lange-Nielsen syndrome, Mohr-Tranebjaerg syndrome, Norrie disease, Treacher Collins syndrome, CHARGE syndrome and Branchio-oto-renal (BOR) syndrome. The genes on the panel have been carefully selected based on scientific literature, mutation databases and our experience.

Our panels are sliced from our high-quality whole exome sequencing data. Please see our sequencing and detection performance table for different types of alterations at the whole exome level (Table).

Assays have been validated for different starting materials including EDTA-blood, isolated DNA (no FFPE), saliva and dry blood spots (filter card) and all provide high-quality results. The diagnostic yield varies substantially depending on the assay used, referring healthcare professional, hospital and country. Blueprint Genetics' Plus Analysis (Seq+Del/Dup) maximizes the chance to find a molecular genetic diagnosis for your patient although Sequence Analysis or Del/Dup Analysis may be a cost-effective first line test if your patient's phenotype is suggestive of a specific mutation type.

Performance of Blueprint Genetics Whole Exome Sequencing (WES) assay. All individual panels are sliced from WES data.

Sensitivity % (TP/(TP+FN) Specificity %
Single nucleotide variants 99.65% (412,456/413,893) >99.99%
Insertions, deletions and indels by sequence analysis
1-10 bps 96.94% (17,070/17,608) >99.99%
11-50 bps 99.07% (957/966) >99.99%
Copy number variants (exon level dels/dups)
Clinical samples (small CNVs, n=52)
1 exon level deletion 92.3% (24/26) NA
2 exons level deletion/duplication 100.0% (11/11) NA
3-7 exons level deletion/duplication 93.3% (14/15) NA
Microdeletion/-duplication sdrs (large CNVs, n=37))
Size range (0.1-47 Mb) 100% (37/37)
Simulated CNV detection
2 exons level deletion/duplication 90.98% (7,357/8,086) 99.96%
5 exons level deletion/duplication 98.63% (7,975/8,086) 99.98%
The performance presented above reached by WES with the following coverage metrics
Mean sequencing depth at exome level 174x
Nucleotides with >20x sequencing coverage (%) 99.4%


The target region for each gene includes coding exons and ±20 base pairs from the exon-intron boundary. In addition, the panel includes non-coding variants if listed above (Non-coding variants covered by the panel). Some regions of the gene(s) may be removed from the panel if specifically mentioned in the ‘Test limitations” section above. The sequencing data generated in our laboratory is analyzed with our proprietary data analysis and annotation pipeline, integrating state-of-the art algorithms and industry-standard software solutions. Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. Our pipeline is streamlined to maximize sensitivity without sacrificing specificity. We have incorporated a number of reference population databases and mutation databases such as, but not limited, to 1000 Genomes Project, gnomAD, ClinVar and HGMD into our clinical interpretation software to make the process effective and efficient. For missense variants, in silico variant prediction tools such as SIFT, PolyPhen, MutationTaster are used to assist with variant classification. Through our online ordering and statement reporting system, Nucleus, the customer has an access to details of the analysis, including patient specific sequencing metrics, a gene level coverage plot and a list of regions with inadequate coverage if present. This reflects our mission to build fully transparent diagnostics where customers have easy access to crucial details of the analysis process.

Clinical interpretation

We provide customers with the most comprehensive clinical report available on the market. Clinical interpretation requires a fundamental understanding of clinical genetics and genetic principles. At Blueprint Genetics, our PhD molecular geneticists, medical geneticists and clinical consultants prepare the clinical statement together by evaluating the identified variants in the context of the phenotypic information provided in the requisition form. Our goal is to provide clinically meaningful statements that are understandable for all medical professionals regardless of whether they have formal training in genetics.

Variant classification is the corner stone of clinical interpretation and resulting patient management decisions. Our classifications follow the Blueprint Genetics Variant Classification Schemes based on the ACMG guideline 2015. Minor modifications were made to increase reproducibility of the variant classification and improve the clinical validity of the report. Our experience with tens of thousands of clinical cases analyzed at our laboratory allowed us to further develop the industry standard.

The final step in the analysis of sequence variants is confirmation of variants classified as pathogenic or likely pathogenic using bi-directional Sanger sequencing. Variant(s) fulfilling all of the following criteria are not Sanger confirmed: 1) the variant quality score is above the internal threshold for a true positive call, 2) an unambiguous IGV in-line with the variant call and 3) previous Sanger confirmation of the same variant at least three times at Blueprint Genetics. Reported variants of uncertain significance are confirmed with bi-directional Sanger sequencing only if the quality score is below our internally defined quality score for true positive call. Reported copy number variations with a size <10 exons are confirmed by orthogonal methods such as qPCR if the specific CNV has been seen less than three times at Blueprint Genetics.

Our clinical statement includes tables for sequencing and copy number variants that include basic variant information (genomic coordinates, HGVS nomenclature, zygosity, allele frequencies, in silico predictions, OMIM phenotypes and classification of the variant). In addition, the statement includes detailed descriptions of the variant, gene and phenotype(s) including the role of the specific gene in human disease, the mutation profile, information about the gene’s variation in population cohorts and detailed information about related phenotypes. We also provide links to the references used, congress abstracts and mutation databases to help our customers further evaluate the reported findings if desired. The conclusion summarizes all of the existing information and provides our rationale for the classification of the variant.

Identification of pathogenic or likely pathogenic variants in dominant disorders or their combinations in different alleles in recessive disorders are considered molecular confirmation of the clinical diagnosis. In these cases, family member testing can be used for risk stratification within the family. In the case of variants of uncertain significance (VUS), we do not recommend family member risk stratification based on the VUS result. Furthermore, in the case of VUS, we do not recommend the use of genetic information in patient management or genetic counseling. For eligible cases, Blueprint Genetics offers a no charge service to investigate the role of reported VUS (VUS Clarification Service).

Our interpretation team analyzes millions of variants from thousands of individuals with rare diseases. Thus, our database, and our understanding of variants and related phenotypes, is growing by leaps and bounds. Our laboratory is therefore well positioned to re-classify previously reported variants as new information becomes available. If a variant previously reported by Blueprint Genetics is re-classified, our laboratory will issue a follow-up statement to the original ordering health care provider at no additional cost.